Survivin is one of the most attractive novel cancer targets. The clinical role of Survivin in cancer has been emphasised by detection of high levels of this protein in almost all tumour types. Elevated expression of Survivin in tumours is generally associated with poor prognosis, increased cancer recurrence and resistance to therapy, both radiation and chemotherapy. The fact that expression of Survivin is, with a few exceptions, not found in normal adult tissues makes Survivin a pivotal cancer gene.
The inhibitor of apoptosis protein (IAP) Survivin is implicated in two key biological events: (i) control of cell proliferation (mitosis), and (ii) regulation of programmed cell death (apoptosis). Additionally, Survivin plays an important role in tumour angiogenesis.
A combination of siRNA targeting Survivin and Taxol results in increased apoptosis induction in SHEP cells compared to siRNA and Taxol alone (Zangemeister-Wittke 2003; Ann. N.Y. Acad. Sci. 1002: 90-94).
Wang et al., 2003; Zhonghua Xue Ye Za Zhi 24, 351-54. “Survivin antisense RNA enhances Taxol-induced apoptosis in leukemia cell line HL-60”.
A wide range of possible antisense LNA oligonucleotides were described in the applicants' earlier international patent application publication No. WO 2004/069991 A2. However, the surprisingly good properties of the LNA oligonucleotides disclosed herein have not yet been described in the prior art.